A serious challenge in today's global health scenario is the wide spread of drug resistant bacterial strains capable of evading even the most recently developed generation of antibiotics (Fait & Tor 2014, Perspect Medicin Chem 6: 25; Michael et al 2014, Front Public Health 2: 145.). Bacteria adopt various strategies to acquire drug resistant phenotypes (Dever & Dermody 1991, Arch Intern Med 151: 886). The bacterial genetic elements provide a number of resistance modalities to the pathogen (Davies & Davies 2010, Microbiol Mol Biol Rev 74: 417). Some genes encode enzymes that are responsible for modifying or degrading the antibiotic while some result in mutation of the antibiotic target enzyme or metabolic process that hinders the interaction of the antibiotic with the target protein. Other genetic elements may decrease the permeability or the uptake of the antibiotic. At times the microbe can activate efflux mechanisms to extrude the antibiotic to the exterior after its uptake. Residing in biofilms, bacteria can efficiently retard the access of antibiotics using the protective matrix as a hindrance (Høiby et al 2010, Int J Antimicrob Agents 35: 322). This leads to establishment of antibiotic gradients conducive for the seeding of resistance. Therefore, development of new strategies is essential to address the threat from multidrug resistant superbugs implicated in various infectious diseases. An astute way forward would be to design molecules that would not only work against existing drug resistant microbes but also reduce the chances of the targeted bacteria to evolve into resistant strains. Such efficacious molecules endowed with features that not only help them act against prevalent resistance but also aid in preventing the development of resistance can be a major advancement in the treatment of microbial diseases caused by both susceptible and/or resistant bacteria.
The present disclosure addresses, in part, these needs of the art.